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Validation of a 16-gene signature for prediction of recurrence after nephrectomy in stage I-III clear cell renal cell carcinoma (ccRCC).

2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2014.32.15_suppl.4502

1527-7755

Bernard Escudier, Serge Koscielny, Margarita Lopatin, Christer Svedman, Virginie Verkarre, C. Radulescu, Y. Neuzillet, Isabelle Hemmerlé, Marc‐Olivier Timsit, Athanasios C. Tsiatis, Michael Bonham, Dejan Knezevic, Thierry Lebrét, Audrey D. Goddard, Arnaud Méjean,

Ferroptosis and cancer prognosis

4502 Background: New molecular diagnostics are needed to improve assessment of recurrence risk after nephrectomy in ccRCC. The 16-gene (11 cancer-related, 5 reference) Recurrence Score (RS) was previously developed in a cohort of 931 stage I-III ccRCC patients (pts) from Cleveland Clinic, requiring validation in an independent study. Methods: A prospective clinical validation study of the Oncotype DX RS in stage I-III ccRCC pts treated with nephrectomy from 1995 to 2007 was conducted by a French consortium. Genes, algorithm, endpoints, methods, and analysis plan were pre-specified and locked prior to merging clinical and molecular data. Gene expression was quantitated by RT-PCR in fixed paraffin-embedded primary ccRCC tissue without knowledge of pt clinical characteristics or outcomes. Recurrence-free interval (RFI, primary endpoint), renal cancer-specific survival (RCSS), disease-free survival (DFS) and overall survival (OS) were analyzed using Cox PH regression stratified by stage with data censored at 5 years, and Kaplan-Meier methods. Results: RT-PCR was successful in 626/645 pts (97%): 398 stage I, 54 stage II, 174 stage III. Median follow up was 5.5 yrs. 5-yr recurrence risk was dependent upon stage (7%, 16% and 30% in stage I, II and III). Continuous RS predicted recurrence risk (HR per 25 point increase in RS (HR/25) = 3.9, 95% CI 2.6-5.8, p<0.001). RS predicted RCSS, DFS and OS (all with p<0.001). In multivariable analyses, RS continued to predict recurrence (HR/25 =2.7, 95% CI 1.6-4.5, p<.001) after adjustment for tumor size, Fuhrman grade and necrosis. RS identified 39% of stage I pts with an average 5-yr recurrence risk of 2% (95% CI 0-7%) and 15% of pts with a 23% (95% CI 13-39%) risk. In stages II-III, RS identified 19% of pts with a 2% (95% CI 0-16%) and 44% of pts with a 39% (95% CI 29-50%) recurrence risk. Conclusions: The 16-gene Oncotype DX RS is validated as a predictor of clinical outcome in pts with stage I-III ccRCC and provides significant information beyond conventional clinical and pathologic characteristics. The RS may be useful to select patients for adjuvant treatment trials, for active surveillance of small renal masses, and for surveillance strategies after surgery.